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Proc Natl Acad Sci U S A. Dec 5, 1995; 92(25): 11553–11557.
PMCID: PMC40440

Systemic immunization with papillomavirus L1 protein completely prevents the development of viral mucosal papillomas.

Abstract

Infection of mucosal epithelium by papillomaviruses is responsible for the induction of genital and oral warts and plays a critical role in the development of human cervical and oropharyngeal cancer. We have employed a canine model to develop a systemic vaccine that completely protects against experimentally induced oral mucosal papillomas. The major capsid protein, L1, of canine oral papillomavirus (COPV) was expressed in Sf9 insect cells in native conformation. L1 protein, which self-assembled into virus-like particles, was purified on CsCl gradients and injected intradermally into the foot pad of beagles. Vaccinated animals developed circulating antibodies against COPV and became completely resistant to experimental challenge with COPV. Successful immunization was strictly dependent upon native L1 protein conformation and L1 type. Partial protection was achieved with as little as 0.125 ng of L1 protein, and adjuvants appeared useful for prolonging the host immune response. Serum immunoglobulins passively transferred from COPV L1-immunized beagles to naive beagles conferred protection from experimental infection with COPV. Our results indicate the feasibility of developing a human vaccine to prevent mucosal papillomas, which can progress to malignancy.

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  • zur Hausen H. Viruses in human cancers. Science. 1991 Nov 22;254(5035):1167–1173. [PubMed]
  • de Villiers EM. Heterogeneity of the human papillomavirus group. J Virol. 1989 Nov;63(11):4898–4903. [PMC free article] [PubMed]
  • Koutsky LA, Galloway DA, Holmes KK. Epidemiology of genital human papillomavirus infection. Epidemiol Rev. 1988;10:122–163. [PubMed]
  • Lorincz AT, Reid R, Jenson AB, Greenberg MD, Lancaster W, Kurman RJ. Human papillomavirus infection of the cervix: relative risk associations of 15 common anogenital types. Obstet Gynecol. 1992 Mar;79(3):328–337. [PubMed]
  • Schiffman MH, Bauer HM, Hoover RN, Glass AG, Cadell DM, Rush BB, Scott DR, Sherman ME, Kurman RJ, Wacholder S, et al. Epidemiologic evidence showing that human papillomavirus infection causes most cervical intraepithelial neoplasia. J Natl Cancer Inst. 1993 Jun 16;85(12):958–964. [PubMed]
  • Bell JA, Sundberg JP, Ghim SJ, Newsome J, Jenson AB, Schlegel R. A formalin-inactivated vaccine protects against mucosal papillomavirus infection: a canine model. Pathobiology. 1994;62(4):194–198. [PubMed]
  • Campo MS, Grindlay GJ, O'Neil BW, Chandrachud LM, McGarvie GM, Jarrett WF. Prophylactic and therapeutic vaccination against a mucosal papillomavirus. J Gen Virol. 1993 Jun;74(Pt 6):945–953. [PubMed]
  • Kirnbauer R, Booy F, Cheng N, Lowy DR, Schiller JT. Papillomavirus L1 major capsid protein self-assembles into virus-like particles that are highly immunogenic. Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):12180–12184. [PMC free article] [PubMed]
  • Rose RC, Bonnez W, Reichman RC, Garcea RL. Expression of human papillomavirus type 11 L1 protein in insect cells: in vivo and in vitro assembly of viruslike particles. J Virol. 1993 Apr;67(4):1936–1944. [PMC free article] [PubMed]
  • Kirnbauer R, Taub J, Greenstone H, Roden R, Dürst M, Gissmann L, Lowy DR, Schiller JT. Efficient self-assembly of human papillomavirus type 16 L1 and L1-L2 into virus-like particles. J Virol. 1993 Dec;67(12):6929–6936. [PMC free article] [PubMed]
  • Hagensee ME, Yaegashi N, Galloway DA. Self-assembly of human papillomavirus type 1 capsids by expression of the L1 protein alone or by coexpression of the L1 and L2 capsid proteins. J Virol. 1993 Jan;67(1):315–322. [PMC free article] [PubMed]
  • Zhou J, Stenzel DJ, Sun XY, Frazer IH. Synthesis and assembly of infectious bovine papillomavirus particles in vitro. J Gen Virol. 1993 Apr;74(Pt 4):763–768. [PubMed]
  • Sundberg JP, O'Banion MK, Schmidt-Didier E, Reichmann ME. Cloning and characterization of a canine oral papillomavirus. Am J Vet Res. 1986 May;47(5):1142–1144. [PubMed]
  • Ghim SJ, Jenson AB, Schlegel R. HPV-1 L1 protein expressed in cos cells displays conformational epitopes found on intact virions. Virology. 1992 Sep;190(1):548–552. [PubMed]
  • Brugge JS, Erikson RL. Identification of a transformation-specific antigen induced by an avian sarcoma virus. Nature. 1977 Sep 22;269(5626):346–348. [PubMed]
  • Lancaster WD, Olson C. Demonstration of two distinct classes of bovine papilloma virus. Virology. 1978 Sep;89(2):372–379. [PubMed]
  • Lim PS, Jenson AB, Cowsert L, Nakai Y, Lim LY, Jin XW, Sundberg JP. Distribution and specific identification of papillomavirus major capsid protein epitopes by immunocytochemistry and epitope scanning of synthetic peptides. J Infect Dis. 1990 Dec;162(6):1263–1269. [PubMed]
  • BREEDIS C, BERWICK L, ANDERSON TF. Fractionation of Shope papilloma virus in cesium chloride density gradients. Virology. 1962 May;17:84–94. [PubMed]
  • Christensen ND, Höpfl R, DiAngelo SL, Cladel NM, Patrick SD, Welsh PA, Budgeon LR, Reed CA, Kreider JW. Assembled baculovirus-expressed human papillomavirus type 11 L1 capsid protein virus-like particles are recognized by neutralizing monoclonal antibodies and induce high titres of neutralizing antibodies. J Gen Virol. 1994 Sep;75(Pt 9):2271–2276. [PubMed]
  • Rose RC, Reichman RC, Bonnez W. Human papillomavirus (HPV) type 11 recombinant virus-like particles induce the formation of neutralizing antibodies and detect HPV-specific antibodies in human sera. J Gen Virol. 1994 Aug;75(Pt 8):2075–2079. [PubMed]
  • Lowy DR, Kirnbauer R, Schiller JT. Genital human papillomavirus infection. Proc Natl Acad Sci U S A. 1994 Mar 29;91(7):2436–2440. [PMC free article] [PubMed]
  • Breitburd F, Kirnbauer R, Hubbert NL, Nonnenmacher B, Trin-Dinh-Desmarquet C, Orth G, Schiller JT, Lowy DR. Immunization with viruslike particles from cottontail rabbit papillomavirus (CRPV) can protect against experimental CRPV infection. J Virol. 1995 Jun;69(6):3959–3963. [PMC free article] [PubMed]
  • Ghim S, Christensen ND, Kreider JW, Jenson AB. Comparison of neutralization of BPV-1 infection of C127 cells and bovine fetal skin xenografts. Int J Cancer. 1991 Sep 9;49(2):285–289. [PubMed]

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